This invention relates to novel prostanoic acid derivatives and processes for the preparation thereof.
The novel prostanoic acid derivatives of this invention are 15-ketals of the naturally occurring prostaglandins and the synthetic analogs thereof. They exhibit a pharmacological spectrum of effectiveness which is similar to that of the natural prostaglandins.
Prostaglandins are C.sub.20 --unsaturated fatty acids having a wide variety of physiological effects (T. O. Oesterling et al, J. Pharmaceutical Sciences 61 (1972) 1861-1895), for example vasodilation, bronchodilation and inhibition of gastric acid secretion. Various natural prostaglandins, such as, for example, prostaglandin E.sub.2 and prostaglandin F.sub.2.sub..alpha., are suitable for inducing abortion and initiation of labor.
The conventional prostaglandins are derivatives of prostanoic acid, which latter has the following formula: ##SPC2##
Examples of known prostaglandins (called PG hereinbelow) having the above basic prostanoic acid structure are: EQU PGE.sub.1 (.DELTA..sup.13 --9--keto--11.alpha., 15.alpha.-diol), EQU PGF.sub.1.sub..alpha. (.DELTA..sup.13 --9.alpha.,11.alpha.,15.alpha.-triol) and EQU PGA.sub.1 (.DELTA..sup.10,13 --9--keto--15.alpha.--ol).
PGE.sub.2, PGF.sub.2.sub..alpha., PGA.sub.2, like the compounds of the PG.sub.1 series also have the above basic structure, except the linkage of the carbon atoms C-5 and C-6 is different. In the PG'.sub.2 series, the C-5 and C-6 atoms are linked by a cis-double bond.
Thus, PG'F.sub.2.sub..alpha. is a .DELTA..sup.5,13 --9.alpha.,11.alpha.,15.alpha.-triol of the above basic structure.
PGE.sub.3, PGF.sub.3.sub..alpha., and PGA.sub.3 differ from the corresponding PG.sub.2 compounds in that the C-17 and C-18 carbon atoms are linked by a cis-double bond. PGF.sub.3.sub..alpha. is a .DELTA..sup.5,13,17 --9.alpha.,11.alpha.,15.alpha.-triol of the above basic structure.
It is generally known that the physiological effects of the prostaglandins are only of a short duration in the mammal organism as well as in vitro. One reason for the rapid loss in effectiveness is seen in that a physiologically inactive metabolite is formed by the oxidation of the 15.alpha.-hydroxy group. Thus, a 13,14-dihydro-15-dehydro derivative is formed, for example, from PGF.sub.2.sub..alpha., i.e., a .DELTA..sup.5 --15--keto-9.alpha.,11.alpha.-diol of the above basic structure. (E. Granstroem and B. Samuelson, Eur. J. Biochem. 10 (1969) 411), which possesses the physiological effects typical for this class of substances only to a very greatly reduced extent.
Attempts have been made to inhibit the metabolizing of the 15-hydroxy group by the introduction of alkyl groups at the C-15 and/or C-16 atoms. (See German Unexamined Laid-Open Applications DOS 2,217,044; 2,121,980 and 2,221,301.) However, the synthesis of such alkylated prostaglandins is very expensive since the pure epimers are only obtained by time-consuming separation operations.